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ABSTRACT: Oral administration of 300 mg/l thioacetamide (TAA) for 4 months causes hepatic lesions comparable to those described in alcoholic liver cirrhosis in humans and associated protein-energy malnutrition. In this sense, direct supplementation with monounsaturated fatty acids (MUFAs) and/or polyunsaturated fatty acids (PUFAs) might provide an advantage in the correction of the fatty acid deficiency in these patients. PUFAs are essential components of cell membranes maintaining its fluidity and function, important energy sources, and precursors of eicosanoids. Moreover, these fatty acids also modulate gene transcription, mRNA stability, and cellular differentiation.
Fifty-four female Wistar rats (Interfauna Ibérica, Barcelona, Spain) weighing 110-120 g were used in this study. The animals were divided into two groups: one group was treated with 300 mg/l TAA dissolved in drinking water during 4 months, and the other group, which served as a control, was given water without TAA. To evaluate the changes induced by the administration of TAA for 4 months, TAA-treated (n = 7) and control animals (n = 5) were killed. Then, the TAA treatment was stopped and the rest of the animals in both TAA and control groups were divided into three experimental groups and three control groups which received for 2 weeks different type of diets. Using the TAA-induced liver cirrhosis model in rats, we analysed the effects of dietary supplementation with MUFAs and PUFAs on binuclearity and ultrastructure of hepatocytes. After TAA-induced cirrhosis, we analysed whether dietary supplementation with fatty acids may restore the normal percentage of binucleated cells, as well as the ultrastructure, nuclear area, and nuclear/cytoplasm index of hepatocytes.
Treatment with TAA causes cirrhosis characterized by the appearance of parenchyma nodules and fibrous septae, as well as qualitative and quantitative alterations in liver and plasma lipids. Our results indicate that dietary MUFAs support hepatocyte recovery regarding its ultrastructural and morphometric values. However, PUFAs-enriched diets (n-3 and n-3 + n-6) do not correct hepatomegaly, fibrosis or lipid accumulation. Thus, dietary PUFAs do not enhance hepatocyte recovery from morphological and ultrastructural alterations.
In our experimental model of cirrhosis, dietary supplementation with a high proportion of long-chain PUFAs (n-3 or n-6) negatively influences liver recovery. This negative effect was likely due to the increased susceptibility of cell membranes to lipid peroxidation, together with an alteration in lipid metabolism.
Experimental and Toxicologic Pathology 09/2005; 57(1):65-75. · 2.78 Impact Factor
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ABSTRACT: Dietary nucleotides modulate a number of metabolic processes, including long-chain polyunsaturated fatty acid metabolism. In this study, we evaluated the effect of dietary nucleotides on plasma and liver microsomal fatty acid profiles in a rat model of liver cirrhosis induced by oral intake of thioacetamide.
Fifty-four female Wistar rats were assigned to one of the following groups: rats in the thioacetamide group (n=45) were given 300 mg thioacetamide/l in their drinking water for 4 months, and rats in the control group (n=9) received water during the same period. After 4 months of treatment, 9 rats in each group were killed. The remaining rats in the thioacetamide group were divided into two new groups, and the animals in each were allowed to recover for 1 or 2 weeks on either a nucleotide-free diet or the same diet supplemented with 50 mg of each of the following: AMP, GMP, CMP, IMP and UMP per 100 g diet.
Saturated (mainly stearic acid), monounsaturated, and n-6 long-chain polyunsaturated fatty acids (mainly arachidonic acid), and also the unsaturation index decreased in plasma of rats with experimental cirrhosis. Administration of the diet supplemented with nucleotides to thioacetamide-treated rats corrected plasma levels of saturated, n-6 long-chain polyunsaturated fatty acids and the unsaturation index. In liver microsomes, the cirrhotic rats showed lower levels of protein and higher levels of palmitic, oleic, linoleic and arachidonic acids. Protein concentrations and levels of all the above-mentioned fatty acids were corrected with the nucleotide-enriched diet.
Dietary nucleotides contribute to correcting plasma and liver microsomal fatty acid alterations in rats with liver cirrhosis induced by chronic oral administration of thioacetamide.
Journal of Hepatology 05/1998; 28(4):662-9. · 9.26 Impact Factor
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ABSTRACT: Patients with liver cirrhosis frequently show some degree of protein-energy malnutrition and obviously require nutritional support. In this study, the treatment of rats consisted of the ad libitum oral intake of a 300 mg/liter thioacetamide solution, used as drinking water for four months. Thioacetamide treatment produced a severe alteration in the plasma fatty acid profile with significant decreases of these, which mimicked changes described in human cirrhosis. This hepatotoxic agent causes nodular cirrhosis, with loss of the normal architecture of the liver and disruption of the vascular pattern. The goal of the study was to evaluate the influence of n-3 and n-6 series long-chain polyunsaturated fatty acid dietary supplementation in experimental animals and to assess the effects of those dietary components on structural recovery in the liver. Significant increases of saturated and monounsaturated fatty acids as well as n-6 polyunsaturated fatty acids were seen only in the animals given the n-6 polyunsaturated fatty acid supplemented diet. However, only rats given the standard diet exhibited some degree of histological regeneration.
Digestive Diseases and Sciences 02/1996; 41(1):197-207. · 2.12 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the dietary supplementation with omega-3 and omega-6 long-chain polyunsaturated fatty acids on the fatty acid composition of plasma and red blood cell membranes in rats with thioacetamide-induced liver cirrhosis.
Thirty-eight female Wistar rats were given 300 mg thioacetamide/L in drinking water for 4 months to induce the experimental liver cirrhosis. Sixteen rats were used as controls. After treatment with thioacetamide, nine rats of each group were killed. Then, thioacetamide-treated rats were divided into three new groups, each receiving a different diet for 2 weeks: a semipurified diet (n = 9), the same diet supplemented with omega-3 long-chain polyunsaturated fatty acids (n = 10), or the same semipurified diet supplemented with omega-3 and omega-6 long-chain polyunsaturated fatty acids simultaneously (n = 10). The remaining control rats were fed the semipurified diet. Liver histology and plasma and erythrocyte fatty acid composition were assessed.
An apparent improvement of the histological damage took place in the rats fed the omega-3+ omega-6-supplemented diet. The diet supplemented with polyunsaturated fatty acids of the omega-3 series induced increases in the omega-3 long-chain polyunsaturated fatty acid levels in total plasma lipids, plasma lipid fractions and in erythrocyte phospholipids, and decreases in omega-6 long-chain polyunsaturated fatty acids in erythrocyte phospholipids during the recovery of rats with thioacetamide-induced liver cirrhosis. The administration of the diet supplemented with both omega-3 and omega-6 long-chain polyunsaturated fatty acids contributed to increase the levels of total plasma saturated, monounsaturated, and omega-6 long-chain polyunsaturated fatty acids from cirrhotic rats.
We conclude that the simultaneous supply of long-chain fatty acids of the omega-3 and the omega-6 series can be beneficial to improve the fatty acid status of this experimental model of liver cirrhosis.
Journal of Parenteral and Enteral Nutrition 19(6):461-9. · 3.29 Impact Factor
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ABSTRACT: Oral administration of 300 mg/l thioacetamide (TAA) for 4 months causes hepatic lesions comparable to those described in alcoholic liver cirrhosis in humans and associated protein-energy malnutrition. In this sense, direct supplementation with monounsaturated fatty acids (MUFAs) and/or polyunsaturated fatty acids (PUFAs) might provide an advantage in the correction of the fatty acid deficiency in these patients. PUFAs are essential components of cell membranes maintaining its fluidity and function, important energy sources, and precursors of eicosanoids. Moreover, these fatty acids also modulate gene transcription, mRNA stability, and cellular differentiation.Methods: Fifty-four female Wistar rats (Interfauna Ibérica, Barcelona, Spain) weighing 110–120 g were used in this study. The animals were divided into two groups: one group was treated with 300 mg/l TAA dissolved in drinking water during 4 months, and the other group, which served as a control, was given water without TAA. To evaluate the changes induced by the administration of TAA for 4 months, TAA-treated (n=7) and control animals (n=5) were killed. Then, the TAA treatment was stopped and the rest of the animals in both TAA and control groups were divided into three experimental groups and three control groups which received for 2 weeks different type of diets. Using the TAA-induced liver cirrhosis model in rats, we analysed the effects of dietary supplementation with MUFAs and PUFAs on binuclearity and ultrastructure of hepatocytes. After TAA-induced cirrhosis, we analysed whether dietary supplementation with fatty acids may restore the normal percentage of binucleated cells, as well as the ultrastructure, nuclear area, and nuclear/cytoplasm index of hepatocytes.Results: Treatment with TAA causes cirrhosis characterized by the appearance of parenchyma nodules and fibrous septae, as well as qualitative and quantitative alterations in liver and plasma lipids. Our results indicate that dietary MUFAs support hepatocyte recovery regarding its ultrastructural and morphometric values. However, PUFAs-enriched diets (n-3 and n-3+n-6) do not correct hepatomegaly, fibrosis or lipid accumulation. Thus, dietary PUFAs do not enhance hepatocyte recovery from morphological and ultrastructural alterations.Conclusions: In our experimental model of cirrhosis, dietary supplementation with a high proportion of long-chain PUFAs (n-3 or n-6) negatively influences liver recovery. This negative effect was likely due to the increased susceptibility of cell membranes to lipid peroxidation, together with an alteration in lipid metabolism.
Experimental and Toxicologic Pathology.
